title: Design, synthesis and antiproliferative evaluation of fluorenone analogs with DNA topoisomerase I inhibitory properties.
abstract: A series of 2,7-diamidofluorenones were designed, synthesized, and screened by SRB assay. Some synthesized compounds exhibited antitumor activities in submicromolar range. Ten compounds (3a, 3b, 3c, 3g, 3j, 3l, 4a, 4h, 4i, and 4j) were also selected by NCI screening system and 3c (GI50=1.66 μM) appeared to be the most active agent of this series. Furthermore, 3c attenuated topoisomerase I-mediated DNA relaxation at low micromolar concentrations. These results indicated that fluorenones have potential to be further developed into anticancer drugs.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Lee
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Huang
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.forename: Tsung-Chih
authors.initials: TC
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Lo
authors.forename: Jih-Hwa
authors.initials: JH
authors.lastname: Guh
authors.forename: Hsu-Shan
authors.initials: HS
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D013329:Structure-Activity Relationship; D013994:Tilorone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D013994:Tilorone
keywords: Fluorenones; NCI 60-cell panel assay; Tilorone; Topoisomerase I